This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Mechanosensitive (MS) ion channels serve as molecular switches, opening and closing in response to stress conveyed through the cellular membrane [1, 2]. In bacteria, MS channels of small conductance (MscS) are thought to act as safety valves preventing cell burst upon osmotic shocks [3, 4]. (http://www.ks.uiuc.edu/Research/MscSchannel/). The two crystal structures of MscS [5, 6, 7], although representing different putative states of the transmembrane (TM) domain, depict the same architecture for MscS' large cytoplasmic domain (CD).